The long-term aim is to understand the mechanisms involved in the response of retinal photoreceptors to light. Such a basic understanding is expected to have eventual clinical significance in cases of retinal dysfunction. At present it is known that illumination leads to a reduction in the sodium permeability of the photoreceptor's plasma membrane, which in turn leads to the electrical response in the cell and to subsequent transmission of information to higher levels of the retina. However, the details of the biochemical steps linking photon absorption to the reduction in sodium permeability are poorly understood. It is suspected that both cyclic guanosine monophosphate (cyclic GMP) and calcium ions are involved, but the precise mechanisms are obscure. One of the immediate aims of the project is to clarify the role of calcium, i.e. to determine whether its level alters during illumination, whether it is involved in excitation and/or light adaptation, and how its level is controlled. A second aim is to investigate the role and effects of cyclic GMP, both on isolated patches of membrane and in the intact photoreceptor, and to attempt to correlate this with the known cyclic nucleotide metabolism of the cell. The experimental technique involves drawing the light-sensitive outer segment of a single photoreceptor into a tiny glass "suction pipette", which is used to record the cell's electrical response, while simultaneously using a "patch pipette" to introduce drugs into the cytoplasm. A sophisticated experimental setup, built around an inverted microscope, is necessary to accomplish this.